Functional Nucleic-Acid-Decorated Spherical Nanoparticles: Preparation Strategies and Current Applications in Cancer Therapy.

Functional nucleic acids (FNAs) have drawn widespread attention in the construction of functional nanomaterials for biomedical applications due to their inherent biological functions and sequence programmability, as well as high thermal stability and easy chemical modification. FNA-decorated spherical nanoparticles (FSNPs) are composed of a metal/metal-free spherical core and a radially oriented FNA shell. Attracted by their unique capabilities, such as resistance to nuclease degradation and capability of crossing the blood-brain barrier, FSNPs as smart nanomaterials for cancer therapy are reviewed. The preparation strategies of FSNPs are first summarized, and the applications of responsive linkers in stimuli-responsive drug release are introduced. The FSNPs are categorized into aptamer-, i-motif-, DNAzyme-, antisense oligonucleotide-, and CpG oligodeoxynucleotide-decorated SNPs. Their applications in cancer therapy include tumor-targeting drug delivery and controllable releasing of drugs, overcoming physiological or pathological obstacles such as blood-brain barrier and interstitial transport barriers, as well as a reversal of resistance to chemotherapy and antitumor immune response activation. The remaining challenges and future directions of FSNPs are also discussed and proposed.